期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 207, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2020.111254
关键词
TBBPA; Proliferation; I kappa B; Ubiquitination; Inflammation
资金
- Taishan Scholars Program of Shandong Province [tsqn201909101]
- National Natural Science Foundation of China [21976114, 91943301]
- Shanxi Province Science Foundation for Youths [201701D221244]
The study found that TBBPA significantly induced proliferation of Ishikawa cells by activating NF-κB and mediating the upregulation of inflammatory cytokines through IκB' degradation. In vivo experiments confirmed the mechanism, suggesting that ubiquitin-mediated IκB' degradation and inflammatory response may serve as critical biomarkers for TBBPA-induced endometrial carcinoma.
Tetrabromobisphenol A (TBBPA), one of the highly common industrial brominated flame retardants (BFRs), has been recently reported to influence the progression of endometrial carcinoma. However, the underlying mech-anism between them has not been fully illuminated. Our findings demonstrated that treatment with low concentrations of TBBPA significantly induced the proliferation of Ishikawa cells in a concentrationand time dependent manner. Mechanically, TBBPA stimulation led to the elevation of NF-kappa B expression, accompanied by the occurrence of ubiquitin-mediated I kappa B ' degradation. Additionally, the upregulation of pro-inflammatory cytokines upon TBBPA exposure was observed in both mRNA and protein levels. Interestingly, the above toxic effects of TBBPA on Ishikawa cells were markedly attenuated by the addition of MG-132, a proteasome inhibitor, suggesting the crucial role of ubiquitin-mediated IxB ' degradation in the TBBPA-stimulated proliferation of Ishikawa cells. Confirmation using in vivo model was also presented in this work. Accordingly, our data indicated that ubiquitin-mediated I kappa B ' degradation and inflammatory response could serve as critical and sensitive biomarkers for the TBBPA-induced endometrial carcinoma, which would be helpful for the future carcinogenic risk assessments of TBBPA exposure on uterus.
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